Affordable Access

deepdyve-link
Publisher Website

A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-alpha levels.

Authors
  • Bos, Steffan D
  • Lakenberg, Nico
  • van der Breggen, Ruud
  • Houwing-Duistermaat, Jeanine J
  • Kloppenburg, Margreet
  • de Craen, Anton J M
  • Beekman, Marian
  • Meulenbelt, Ingrid
  • Slagboom, P Eline
Type
Published Article
Journal
European Journal of Human Genetics
Publisher
Springer Nature
Publication Date
Aug 01, 2010
Volume
18
Issue
8
Pages
953–959
Identifiers
DOI: 10.1038/ejhg.2010.52
PMID: 20407468
Source
Medline
License
Unknown

Abstract

Cytokines are major immune system regulators. Previously, innate cytokine profiles determined by lipopolysaccharide stimulation were shown to be highly heritable. To identify regulating genes in innate immunity, we analyzed data from a genome-wide linkage scan using microsatellites in osteoarthritis (OA) patients (The GARP study) and their innate cytokine data on interleukin (IL)-1beta, IL-1Ra, IL-10 and tumor necrosis factor (TNF)alpha. A confirmation cohort consisted of the Leiden 85-Plus study. In this study, a linkage analysis was followed by manual selection of candidate genes in linkage regions showing LOD scores over 2.5. An single-nucleotide polymorphism (SNP) gene tagging method was applied to select SNPs on the basis of the highest level of gene tagging and possible functional effects. QTDT was used to identify the SNPs associated with innate cytokine production. Initial association signals were modeled by a linear mixed model. Through these analyses, we identified 10 putative genes involved in the regulation of TNFalpha. SNP rs6679497 in gene CD53 showed significant association with TNFalpha levels (P=0.001). No association of this SNP was observed with OA. A novel gene involved in the innate immune response of TNFalpha is identified. Genetic variation in this gene may have a role in diseases and disorders in which TNFalpha is closely involved.

Report this publication

Statistics

Seen <100 times